The mechanisms which underlie the selective vulnerability of various central nervous system structures to hypoxic-ischemic injury will be studied in rabbits subjected to a standardized hypoxic-ischemic insult. The insult will consist of unilateral common carotid artery ligation combined with arterial hypoxemia at one of two levels (PaO2 20- 25 and 26-30 mm Hg) for thirty minutes, with maintenance of normal blood pressure. Regional cerebral blood flow will be assessed by means of the C14-antipyrine autoradiographic method. Regional brain glucose metabolism will be measured autoradiographically by means of C14-2- deoxyglucose, an incompletely metabolized glucose congener. In a matched series of chronically surviving animals histological examination of the brain will be performed. Patterns of altered regional blood flow and metabolism will be correlated with each other and with histological changes. Although specific regions of the central nervous system are believed to be particularly vulnerable to the effects of oxygen deprivation, the available data are insufficient in most cases to differentiate intrinsic regional tissue vulnerability from vulnerability secondary to regional blood flow impairments. This study will help clarify the pathogenesis of the neuropathological changes seen in patients following hypoxic-ischemic insults such as may occur in the settings of cardiac arrest, anesthesia accidents, respiratory insufficiency, various industrial intoxications, etc. The data will direct attention to the physiological mechanisms involved in regional brain injury in these settings and will provide extensive documentation of a reproducible model of hypoxia-ischemia in which the potential effectiveness of various drug therapies, etc., may subsequently be assessed and quantitated.